High-Frequency Stimulation of the Centromedian Thalamic Nucleus Aborts Seizures and Ictal Apnea.

SUMMARY: A 32-year-old right-handed woman presented with medically and surgically refractory left temporal neocortical epilepsy secondary to focal cortical dysplasia who underwent stereoelectroencephalography involving the centromedian nucleus of the thalamus. With the use of real-time stereoelectroencephalography monitoring, four electroclinical seizures were aborted by administering high-frequency stimulation at the centromedian nucleus at seizure onset. Seizures before stimulation were all associated with ictal apnea, while those with stimulation had no ictal apnea. This case demonstrates how providing high-frequency stimulation to the centromedian nucleus of the thalamus can abort electroclinical seizures and ictal apnea.

The immune system and metabolic products in epilepsy and glioma-associated epilepsy: emerging therapeutic directions.

Epilepsy has a profound impact on quality of life. Despite the development of new antiseizure medications (ASMs), approximately one-third of affected patients have drug-refractory epilepsy and are nonresponsive to medical treatment. Nearly all currently approved ASMs target neuronal activity through ion channel modulation. Recent human and animal model studies have implicated new immunotherapeutic and metabolomic approaches that may benefit patients with epilepsy. In this Review, we detail the proinflammatory immune landscape of epilepsy and contrast this with the immunosuppressive microenvironment in patients with glioma-related epilepsy. In the tumor setting, excessive neuronal activity facilitates immunosuppression, thereby contributing to subsequent glioma progression. Metabolic modulation of the IDH1-mutant pathway provides a dual pathway for reversing immune suppression and dampening seizure activity. Elucidating the relationship between neurons and immunoreactivity is an area for the prioritization and development of the next era of ASMs.

Adverse Childhood Experiences in Patients With Neurologic Disease.

Background and Objectives: To describe the prevalence of high adverse childhood experiences (ACEs) among neurology outpatients and determine their association with health care utilization rates and comorbid medical and psychiatric disease. Methods: This was a cross-sectional study of adults seen for outpatient neurology follow-up at the University of Pennsylvania. Participants completed the ACE questionnaire and depression/anxiety screenings. Health care utilization metrics (emergency department [ED] visits, hospitalizations, and outpatient calls) were obtained for all participants. High ACE scores were defined as a score of ≥4. The prevalence of high ACE scores in our cohort was compared with US historical controls. Statistical associations were adjusted for age, sex, and race/ethnicity. Results: One hundred ninety-eight patients were enrolled in the study. Neurology patients were more likely to have elevated ACE scores compared with US population estimates (23.7% vs 12.6%, p < 0.01). High ACE scores were associated with increased ED utilization (odds ratio [OR] = 21, 95% CI [5.8-76.0], p < 0.01), hospitalizations (OR = 5.2, 95% CI [1.7-15.0], p < 0.01), and telephone encounters (OR 3, 95% CI [1.1-8.2], p < 0.05). High ACEs were also associated with medical and psychiatric comorbidities (OR 5.8, 95% CI [2.0-17.0], p < 0.01 and OR 4.5, 95% CI [2.1-9.6], p < 0.01) and high depression and anxiety scores (OR = 6.9, 95% CI [2.8-17.0], p < 0.01, and OR = 4.3, [95% CI 1.7-11.0], p < 0.01). Discussion: Patients with neurologic conditions are more likely to have high ACEs than the US population, which was associated with higher rates of health care utilization, increased number of medical and psychiatric comorbidities, and higher anxiety and depression scores. Addressing ACEs may be a way to improve the health outcomes of patients with neurologic conditions.

Standardized Transfer Process for a Neurointensive Care Unit and Assessment of Patient Bounceback.

BACKGROUND: Patients who require readmission to an intensive care unit (ICU) after transfer to a lower level of care ("bounceback") suffer from increased mortality and longer hospital stays. We aimed to create a multifaceted standardized transfer process for patients moving from the neurointensive care unit (neuro-ICU) to a lower level of care. We hypothesized that this process would lead to improvement in provider-rated safety and a decreased rate of bouncebacks to the neuro-ICU after transfer. METHODS: The study took place at the Hospital of the University of Pennsylvania from October 2018 to October 2020. A standardized five-step transfer process was created and implemented for transferring patients from the neuro-ICU to a lower level of care. Patient care providers completed a survey before and after implementation of the protocol to assess a variety of components related to safety concerns when transferring patients. The rate of bouncebacks pre and post intervention was calculated by using a two-sample Wilcoxon rank-sum test, and disposition at discharge was calculated by using Fisher's exact test. RESULTS: Of the 1176 total patient transfers out of the neuro-ICU, 29 patients bounced back within 48 h. The average age of patients who bounced back was 63.3 years old, with a similar distribution among men and women. The most common reason for bounceback was respiratory distress, followed by cardiac arrhythmia, stroke, and sepsis. Implementation of the standardized process led to a decrease in provider-rated concern of overall safety (5 to 3, p = 0.008). There was improvement in transfer delays due to bed availability (3 to 4.5, p = 0.020), identification of high-risk patients (5 to 6, p = 0.021), patient assignment to the appropriate level of care (5 to 6, p = 0.019), and use of the electronic medical record handoff indicator (5 to 6, p = 0.003). There was no statistically significant difference in terms of patient bounceback rate after implementation of the process (2.4% vs. 2.5%, p = 1.00) or patient disposition at discharge (p = 0.553). CONCLUSIONS: Patients who bounceback to the neuro-ICU within 48 h had an increased length of hospital stay, had an increased length of ICU stay, and were more likely to be intubated for more than 96 h. Implementation of a standardized five-step transfer process from the neuro-ICU to a lower level of care resulted in improvement in multiple provider-rated safety outcomes and identification of high-risk patients but led to no difference in the patient bounceback rate or patient disposition at discharge.

Pseudotumor Cerebri Syndrome Complicated by Diffuse Ophthalmoparesis and Polyradiculopathy.

Pseudotumor cerebri syndrome (PTCS), also known as idiopathic intracranial hypertension (IIH), is defined by elevated intracranial pressure in the absence of a structural or cerebrospinal fluid (CSF) abnormality. Typical features include headache, visual symptoms, and pulsatile tinnitus. Cranial nerve deficits are seen in a minority of cases, most often sixth nerve palsies. We present a unique cause of PTCS complicated by diffuse ophthalmoparesis and polyradiculopathy. A 27-year-old healthy woman presented with 2 weeks of blurry vision, diplopia, and facial and arm weakness. On examination, she had decreased visual acuity, markedly constricted visual fields in both eyes, with severe bilateral optic disc edema on fundus examination. There was diffuse ophthalmoparesis, right upper and lower facial weakness, and bilateral arm weakness. Magnetic resonance imaging brain revealed optic disc protrusion and a partially empty sella but no other abnormalities. Electromyogram (EMG) was consistent with bilateral C5-6 radiculopathies. Lumbar puncture revealed an opening pressure of 56 cm H2O with otherwise normal CSF constituents. She was treated with high-dose acetazolamide and methylprednisolone followed by optic nerve sheath fenestration. Due to progressive vision loss, she ultimately required ventriculoperitoneal shunting, after which her papilledema, ophthalmoparesis, and facial and arm weakness rapidly improved. This is a unique case of PTCS associated with diffuse ophthalmoparesis and polyradiculopathy. This constellation of abnormalities usually suggests an underlying inflammatory process in the subarachnoid space. However, once this has been excluded, the possibility of PTCS should be considered as early treatment can result in rapid reversal of symptoms and preserve visual function.

Association of Autonomic Storming with Urinary Catheter Removal in NMDA Receptor Encephalitis: A Case Report.

We present a case of a 47-year-old female who presented with altered mental status and was found to have severe anti-NMDA receptor encephalitis. Her intensive care unit course was complicated by paroxysmal sympathetic storming. She also had urinary retention for which a catheter was placed early in her admission, but attempts at removal were associated with worsening storming. Her average Clinical Features Scale score was 5.9 when the catheter was not in place compared to 3.6 with the catheter in place. This is the first case report to our knowledge demonstrating an association between urinary catheter removal and autonomic storming in anti-NMDA receptor encephalitis.

Cerebral fat embolism syndrome in sickle cell disease without evidence of shunt.

Fat embolism syndrome (FES) is a known complication of sickle cell disease (SCD) that occurs secondary to vaso-occlusive crises, bone marrow infarction, and the subsequent release of fat globules into the venous circulation. Although neurologic involvement is common, the pathophysiology of cerebral fat emboli remains controversial. While fat microemboli can enter the arterial circulation through right-to-left shunts, the systemic release of free fatty acids may also cause indirect endothelial damage and disruption of the blood-brain-barrier. We present an unusual case of cerebral fat emboli in SCD that occurred in the absence of acute chest syndrome or right-to-left shunt, favoring a biochemical etiology. Treatment of FES includes supportive care and emergent red cell exchange transfusions.

FACETS of health disparities in epilepsy surgery and gaps that need to be addressed.

PURPOSE OF REVIEW: Disparities in treatment and outcomes of patients with epilepsy have been identified in several distinct patient populations. The purpose of this review is to organize the literature and establish clear pathways as to why certain patient populations are not receiving epilepsy surgery. By establishing the acronym FACETS (fear of treatment, access to care, communication barriers, education, trust between patient and physician, and social support), we set up a pathway to further study this area in an organized fashion, hopefully leading to objective solutions. RECENT FINDINGS: Studies revealed that African American, Hispanic, and non-English-speaking patients underwent surgical treatment for epilepsy at rates significantly lower compared to white patients. SUMMARY: This article explains possible reasons outlined by FACETS for the health disparities in epilepsy surgery that exist in patients of a certain race, socioeconomic status, and language proficiency.

Occipital dysembryoplastic neuroepithelial tumor presenting as adult-onset temporal epilepsy.

Dysembryoplastic neuroepithelial tumor (DNET) is a benign brain tumor which commonly presents as childhood-onset temporal lobe epilepsy (TLE). We present a case of histologically proven DNET with a clinical presentation and scalp EEG suggestive of adult-onset TLE. MRI showed an occipital lesion. PET showed abnormal metabolism of the occipital lesion and the ipsilateral temporal lobe; raising concern for an abnormal functional network reorganization. Intracranial EEG showed interictal spikes and seizures originating from the occipital lesion with no seizures emanating from the temporal lobe. Occipital DNET due to their chronic nature can reorganize the network and mimic TLE.

Neurogenesis is enhanced by stroke in multiple new stem cell niches along the ventricular system at sites of high BBB permeability.

Previous studies have established the subventricular (SVZ) and subgranular (SGZ) zones as sites of neurogenesis in the adult forebrain (Doetsch et al., 1999a; Doetsch, 2003a). Work from our laboratory further indicated that midline structures known as circumventricular organs (CVOs) also serve as adult neural stem cell (NSC) niches (Bennett et al., 2009, 2010). In the quiescent rat brain, NSC proliferation remains low in all of these sites. Therefore, we recently examined whether ischemic stroke injury (MCAO) or sustained intraventricular infusion of the mitogen bFGF could trigger an up-regulation in NSC proliferation, inducing neurogenesis and gliogenesis. Our data show that both stroke and bFGF induce a dramatic and long-lasting (14day) rise in the proliferation (BrdU+) of nestin+Sox2+GFAP+ NSCs capable of differentiating into Olig2+ glial progenitors, GFAP+nestin-astrocyte progenitors and Dcx+ neurons in the SVZ and CVOs. Moreover, because of the upsurge in NSC number, it was possible to detect for the first time several novel stem cell niches along the third (3V) and fourth (4V) ventricles. Importantly, a common feature of all brain niches was a rich vasculature with a blood-brain-barrier (BBB) that was highly permeable to systemically injected sodium fluorescein. These data indicate that stem cell niches are more extensive than once believed and exist at multiple sites along the entire ventricular system, consistent with the potential for widespread neurogenesis and gliogenesis in the adult brain, particularly after injury. We further suggest that because of their leaky BBB, stem cell niches are well-positioned to respond to systemic injury-related cues which may be important for stem-cell mediated brain repair.